ArticleNature chemical biology2017
The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
107 citing papers in PubMed, 232 citations in OpenAlex.
- Inhibition of EED enhances osteogenic differentiation and bone formation: a potential therapeutic strategy for osteogenesis imperfecta.JBMR plus · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- The Role of EZH2 ın Malıgnant Pleural Mesothelıoma and Beyond: Current Practıce and Future Perspectıves.Current oncology reports · 2026Review
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- CRISPR-Cas9 screen reveals that inhibition of enhancer of zeste homolog 2 sensitizes malignant T cells to dimethyl-fumarate-induced cell death.The FEBS journal · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Oncogenic and immunomodulatory functions of SUV420H1 in HPV-negative head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- An evolving landscape of PRC2-RNA interactions in chromatin regulation.Nature reviews. Molecular cell biology · 2025Review
- Inhibition of EED-mediated histone methylation alleviates neuroinflammation by suppressing WNT-mediated dendritic cell migration.Journal of neuroinflammation · 2025Article
- A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.Cell reports · 2025Article
- A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.Journal of medicinal chemistry · 2025Article
- CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.Scientific reports · 2025Article
- Review
- Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems.Nature neuroscience · 2024Article
- Control of endothelial cell function and arteriogenesis by MEG3:EZH2 epigenetic regulation of integrin expression.Molecular therapy. Nucleic acids · 2024Article
- Overcoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy.Cancer discovery · 2024Article
- Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics.Drug discovery today · 2024Review
- A miniaturized mode-of-action profiling platform enables high throughput characterization of the molecular and cellular dynamics of EZH2 inhibition.Scientific reports · 2024Article
- DOT1L interaction partner AF10 controls patterning of H3K79 methylation and RNA polymerase II to maintain cell identity.Stem cell reports · 2023Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
38 authors at 2 institutions in 2 countries.
Funding
Abstract
Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. Phenotypic effects observed in vitro and in vivo are similar to those of known PRC2 enzymatic inhibitors; however, A-395 retains potent activity against cell lines resistant to the catalytic inhibitors. A-395 represents a first-in-class antagonist of PRC2 protein-protein interactions (PPI) for use as a chemical probe to investigate the roles of EED-containing protein complexes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.